Assisted Fertility
Speakers: Dr. Maria Bustillo (click here for biography)
Soap Summit 4

Transcript of Proceedings
October 9, 1999

SONNY FOX: Dr. Maria Bustillo, who is a Cuban American, is Director of Assisted Reproductive Technology Services with the South Florida Institute for Reproductive Medicine. She has served as President of the Society of Associated Reproductive Technologies, and the Gyneco Radiology Society. She's currently Vice President for The Society for the Advancement of Women's Health Research and so on. She's written a number of papers. She is often quoted in magazines and newspapers, and was quoted in the New York Times as a matter of fact, last week in this area.

We are delighted that Dr. Bustillo was able to fly up here and be with us to take off from the discussion we've had so far, and get into the question of what are these ethical questions connected with Assisted Fertility Reproduction. Dr. Bustillo.

DR. MARIA BUSTILLO: Thank you very much. This is a daunting task to do in 20 minutes but I'm going to try. And., I want to thank Lynn for a wonderful presentation. I've been intimately involved in the gathering of that data as she knows. This has been coming for about ten years. Actually the Society for Assisted Reproductive Technology which I was President of in '94 was instrumental in starting this before we had the law in 1987. So it's one of the few professional organizations that's actually had this in place for a long, long time.

We are accountable for what we do or we try to be. Anyway, if I could have the first slide and talk a little bit about why we do ART, and then some of the unique things that ART represents to me. I have been very fortunate. I'm a lot older than I appear, and I was involved in the first egg donation in the United States in 1983. I've been involved in ART since 1981. The first baby in ART was born in '81 in this country, so I have been fortunate to see the progress of this field both from a technical, medical and a social and ethical point of view. It gives me a kind of a unique perspective.

We talk about all this high-tech reproduction as though it is easy, but it actually is very complicated. Nature's way of reproducing involves deposition of sperm. The sperm have to work, the eggs have to be ovulated, they have to be produced, etc. So this is an incredibly complicated procedure just naturally. And it's amazing that there's world overpopulation, and that all of us are sitting here. As I always tell the medical students, it's amazing when I explain all this to them - that we're all here.

When somebody presents themselves to me, I have to try to figure out what is actually the problem and how can we fix it? This is a very famous old picture by Frank Netter, and this is just to remind me to tell you about some of the things that Lynn already mentioned about aging. Women are born actually with a lot fewer eggs then we had when we were inside our mothers. Actually our number of eggs peak when we are about 27, 28 weeks in utero, inside our mothers. We have about three to four million eggs in our ovaries.

There's a process that we don't understand by which these eggs die. And when we're actually born we have about 400,000 eggs, it's estimated. But we don't ovulate 400,000 eggs in our lifetime. Our reproductive life lasts about 40 years. And if you think that you ovulate about 12 to 13 times a year, that's not 400,000 eggs. So what happens is a group of eggs develop every month. What happens as we get older is the eggs that are there are fewer in number and less in quality. Hence, some of the problems that we heard about from Beverly in terms of aging.

That's why women over 35, 37, have a very high incidence of unexplained infertility. This does not happen in men unless they have really chronic diseases at very old age. So this is a phenomenon unique to women. As a woman gets older the incidence of infertility goes up. This is the same sort of data that Lynn showed you from previous surveys in the United States where women, as high as 30 percent or more, over the age of 40 are infertile.

Now IVF, Lynn has already explained to you, that requires a number of steps. The first is stimulation of the ovaries to obtain multiple eggs. The egg retrieval has gone from a surgical procedure to a very simple office based procedure with ultrasound guidance. After retrieval of the eggs, the eggs are inseminated. I'm going to talk about some advances in that area and the embryo transfer. The whole procedure takes about 21 to 30 days. Now the most significant aspect that we've already mentioned is the ovarian response to stimulation because that varies depending on the woman's age. And it depends on how she responds to these medications that we give her. That affects the quality of eggs, and the number of eggs, which is very important.

These factors are actually very much interrelated because they determine the quality of the egg, the quality of the embryo and therefore the potential for that embryo to implant, and to give you a live born baby - which is the goal here.

Now why do we use ART? Were talking today about infertility, but I think there's a whole new area that's going to be coming along that I want to mention a little bit at the end of my talk.

We use ART to treat infertility, and to assist fertilization, particularly for those men who have very poor sperm. We use it also to provide eggs and sperm with egg donation, sperm donation when the eggs and sperm are either abnormal or absent - as in the case of sperm and egg donation. We use it sometimes if a woman or a man carry some sort of genetic problem and we can't diagnose is antenatally. What we do is sperm, or egg substitution so we can use somebody else's egg because the woman carries some horrendous disease that she doesn't want to carry on to the next generation. We use it also to actually diagnose genetic disease in the embryo. This is a whole new area of embryo genetics. To be able to choose the embryo that's unaffected, and lead to a pregnancy that doesn't carry whatever genetic trait that we're interested in.

Now, a lot of technologies Lynn already mentioned, and she already said that the majority of them are in-vitro fertilization, over 70 percent. I'm going to talk a little bit about IVF egg donation and embryo cryo-preservation.

Now, how do we choose which technology a patient uses? Well, obviously the cause of infertility is relevant here because if she has very badly diseased tubes, then we're going to go straight to IVF before we do anything else. The age of the women, the status of the gametes, the condition of her uterus, also leads us to hurry up in terms of getting to high tech sooner. Obviously if we have a diseased uterus that's not repairable, then we have to think about a surrogate. Also, very important and very relevant to the older patient is the ability of that woman to withstand pregnancy. Pregnancy is a huge physiologic insult to the body. Although it's natural, it's something that we have to be able to withstand in terms of our cardiovascular system, etc, and we have to be able to withstand pregnancy. This is both from the physical and the mental point of view.

Now, what else influences the choice of ART? Well, obviously a couple has to be comfortable if you're going to involve a third party, so that's very important. And the factors that enter into that are obvious psychosocial factors, ethnic background, religious beliefs, emotional resources as well as financial resources. If a patient doesn't have financial resources she can't get very far. If she doesn't have the emotional resources, it may be against her best interest to really pursue some of these very, very trying treatments. Another consideration is whether their own gametes are available, whether the third party gametes are going to be used, or whether the embryos are going to be donated, whether there's a surrogate, whether it's a host uterus or a third party donor egg as well as a host uterus.

Now, this is a whole social issue that I'm not going to discuss, but who pays for this treatment? If you think about this, this has a great impact on access to treatment for different socio-economic groups as well as the amount of utilization.

It turns out that in some European countries where in-vitro fertilization is covered by their health care system, the population use of IVF is about 400 percent higher than it is in the United States. So some of the social issues then are cost and availability to people, the allocation of resources and insurance coverage impact on the resulting children; also it impacts very importantly on the failure of treatment. And it impacts on the use of a third party. Some of the legal issues have to do with rights and access to records and recipients who are not married. The ownership of the embryos if there is a divorce is another issue, as is the quality assurance of the laboratory. So these are all very, very important issues.

Now what I want to talk to you about some of the novel, more recent techniques and the hope that they offer to infertile couples. I also want to discuss some of the problems that I see with them.

The first is something that you may have read about. It's been around now since 1992. It's call intracytoplasmic sperm injection. Intracytoplasmic sperm injection is the actual placement of a sperm inside an egg and this is used for all kinds of male infertility. I don't have a pointer, but on the left hand here, you can actually see a little dot at the end of the pipette. That's actually a single sperm that has been chosen. Primarily because it moves, we know that it's alive. And that's an egg on the right that's being held by a glass pipette on the left. And you see that needle, it's a fine glass needle entering the egg to actually deposit the sperm into the substance of the egg. This came about by an actual laboratory accident in 1991 in Belgium. The physician laboratory person who did this made the mistake, was trying to deposit the sperm underneath the egg right here. The technique that preceded this one was called sub-zonal injection, which wasn't very good. In doing that, he made the mistake and actually got into the substance of the egg, left the egg alone and the next day lo and behold it fertilized. This was a revolution because this makes it possible for sperm that are incredibly bad to be able to fertilize eggs to a very high rate.

So we have just about conquered male infertility. Unfortunately, for women, like a lot of other things, we've conquered male infertility by treating the woman. He only has to ejaculate into a cup, which is traumatic enough. But she, she has to undergo all of this. But ICSE as we call it, intracytoplasmic sperm ejection can be used, as I said, with ejaculated sperm. It can be used with sperm directly from the epididymis, which is the connection between the testicle and the vas, which is the connection between the outside world and the testicle. Or you can actually extract sperm from the testicle. So men, for instance, who have been vasectomized now, don't have to undergo vasectomy reversals. We can just put a needle into their testicle, take a piece of testicle out, dissect out the sperm and use that on the wife's eggs.

So it's amazing. And all the men are squirming. But the key here though is that there's a relative unimportance now as to the quality of sperm. All they really have to be is there, in low numbers and sometimes we have had the situation where we actually have more eggs in the laboratory than we can find sperm for. It's usually millions and millions of sperm per egg right? But not in some cases of severe male problems. So in this procedure really, the egg number or quality is what determines the success rate of this.

Well what are some of the problems with this? Remember, particularly in men who don't have any kind of obstruction, that they have really bad sperm, we don't know why. Some of the men have problems because there are genetic problems that are inherited. For instance, men with cystic fibrosis. But you can get sperm from their testicles. Or men with vas obstruction can have the cystic fibrosis gene.

The question is whether we're going to make these men able to reproduce and propagate other genetic disorders. So it's an interesting ethical issue. In the men who have really bad sperm, we make them fathers where ordinarily they wouldn't be in a natural situation. We may be propagating this as a problem. In other words, it would generate little boys. They may inherit that Y chromosome. This is something to think about and to worry about. All my friends say, jokingly we're just making more business for ourselves.

All right, I'm going to leave ICSE for a minute and talk to you about something very exciting that you're going to be hearing more about, taking eggs from the ovary. I showed you that picture of the ovary with the little tiny eggs before they were mature. You can actually take an immature egg now from an ovary. You can take it from a biopsy, from what's called a ovariectomy specimen, an ovary being removed for a benign condition. And you can actually take those eggs, and in the laboratory we have ways of maturing those eggs now. You can inseminate them and culture them to embryos, and now we can even freeze them. We are not very far in this technology. This is all very preliminary. You may have heard the story in the New York Times. It was really based on the fact that there's a report of a women having had their ovary removed for a benign condition, and then pieces of it put back and restoring her ovarian function. Think about this from a social point of view and I think the impact of this, as I see it, is going to be wonderful because if it really works well, we won't need to give them all these drugs to stimulate multiple egg production. We don't know what the long-term effects are.

We can also cryopreserve or freeze eggs from women who are at risk of losing their eggs. For instance, women who are undergoing chemotherapy, radiation therapy for certain cancers. They have a very, very high rate of ovarian failure. In other words they go through menopause because these agents actually kill their eggs. If we could remove them and freeze them, and if they recover from their cancer, (which a lot of them will do then we can then either replace their ovaries or somehow do this in the laboratory and create embryos from them.

The other good thing about this is if you can do it with eggs, you don't need a source of sperm, because we used to do this for women with embryos. But if you have a 15-year-old that's going to have major chemotherapy for a non-Hodgkin's lymphoma, she doesn't necessarily have a sperm partner chosen at the age of 15. So if we were going to cryopreserve embryos, you needed to use an external source of sperm. With cryopreserving eggs you don't have to do that. So you don't have generate embryos.

Now, there is a whole other area that I think you'll be hearing a lot about. This is something that I think is going to really expand in the next ten years or so, five to ten years, primarily because of the advent of the Genome Project, we're identifying genes. We'll be able to make diagnoses in embryos with a lot of diseases. The field of reproductive technology and the field of genetics are coming together.

With pre-implantation genetics, the principle is that each cell of the embryo is basically identical before the differentiation really starts. If you take a single cell, you can actually do a diagnostic procedure and assume that the cell that is removed can be tested for chromosome problems or hereditary disorder. That cell basically tells you the status of the entire embryo. And again, you can then choose the embryos to replace.

This is an eight-cell embryo, a beautiful day three embryo. Basically what you would do is you'll take one of the cells and you'll do the analysis, and we have techniques now that are called single cell PCR (polymerase chain reaction) techniques. You can actually amplify the DNA of one cell and you can do a diagnosis for simple diseases like cystic fibrosis, sickle cell anemia, the hemoglobin; for a lot of diseases this has actually already been performed. This is an alternative to actually getting pregnant on your own. If you already know you have a risk for a disease, getting pregnant on your own, then having a prenatal procedure like a chorionic-villi sampling or an amniocentesis to decide whether the embryo, the baby is affected. If it is, then you can have a termination. This is really for people who find termination not palatable, but would go through this. You could do a biopsy of the embryo. That's probably the preferred procedure.

There is an old procedure that we worked on a long time that might be resuscitated for this; it is actually taking the embryo out of the uterus before it implants. There's about a two-day window where you can actually have access to the embryo by flushing it out. But that technique doesn't work very well. If you don't get it, then the patient still gets pregnant and so it's fraught with some problems.

Now what about other areas that are of interest? This is being used for sex selection. One of the reasons this is being used for gender selection is because there's close to 400 diseases that are X linked and that are passed on by the X chromosome. These diseases primarily affect the male fetus, the male babies that are born. You can actually take one of those cells that I showed you, and you can do a procedure called FISH. You can actually identify certain chromosomes and identify whether that fetus is male or female. If you're trying to avoid an X linked disorder, what you would then do is to take the embryos that are female and replace them, discarding the embryos that are male. So, pre-implantation genetic diagnosis, PGD, is being used for sex selection. And it's also being used for family balancing. Family balancing is a fancy word for you want a baby of a certain sex. This is very controversial.

There is a clinic in the United States doing this with sperm sorting. They're separating the sperm that have the X chromosome and the sperm that have the Y chromosome. They are able to achieve, if they want, a female with about 85 percent success. With the male, it's not as good for some reason. Technically the sperm bearing the X bearing sperm actually weighs a little more. It's easier to separate. Again, that would be used for X linked disorders to try to use that sperm for insemination, not ART, and to avoid babies that are of the sex that is not wanted.

So there are obviously different methods for gender selection, and gender selection is something that's being used a lot throughout the world. In certain countries like India and Pakistan and China, gender selection is done with post implantation genetic diagnosis. CVS or amniocentesis is used to decide whether or not you're going to get rid of the fetus, if it's the sex you don't want.

Now let's talk about some of these issues that are really here right now. I'm not going to talk about all of them, but I picked out a few.

I want to talk about the position of abandoned embryos. I want to talk about egg donation in a little more detail, as Lynn already mentioned. Then I want to talk a little bit about posthumous reproduction because that's a topic that's pretty hot.

Now why do we freeze embryos? As Lynn mentioned, if women make a lot of embryos. One of the biggest problems, as she's already mentioned, is the incidence of multiple pregnancy.

So what we try to do when we do IVF is reduce that risk by trying to reduce the number of embryos that we replace. We're still not very good at that because we don't have very many good ways to decide which embryos we'll implant, and the patient has already mortgaged her house. So the pressure is really on us to try to get them pregnant. We take a lot of heat for that, understandably, and we need more research to be able to say this embryo is going to make it. We freeze embryos when we have a lot of embryos in order to reduce the risk of multiple pregnancy.

There is also a condition that is a complication of ART. If the woman stimulates her ovaries so much that she has a problem, she might really get sick with what's called ovarian hyper-stimulation. Her ovaries get very big, her abdomen gets very bloated. She can get quite ill and require hospitalization. If she gets pregnant on top of that, that condition worsens. So in that case we would generally freeze all her embryos, get her over that diseased condition and then thaw the embryos for conception.

What is the legal status of an embryo? This is interesting and I think there is a locus and a scope of this. Who has the right to decide? I don't know the answer to that.

What are the options that you have? I think when we do cryopreservation, most programs have a very long consent form and try to discuss these things with the patient. The ownership and rights and control are very important. You can either discard them or not transfer them. Then the other huge problem is when are embryos abandoned? I was Director at Mt. Sinai here in New York and we had embryos that were about ten years in storage and we had about 15 different sets of embryos of which we could not find their owners, that is the couple.

The question is what was our liability in terms of keeping those embryos frozen? We had made every effort to track down these people and it's really a problem. This became a huge problem in England. About, a year and a half ago when they enforced the law that said they could not keep embryos longer than five years in the freezer. They didn't allow the clinics in England enough time, sufficient time, to track down some of the patients, some of these couples. They ended up discarding a lot of embryos and there was a big public uproar about that.

This is not an insignificant problem. The Ethics Committee at Mt. Sinai decided that ten years is sufficient. If in ten years the person hadn't claimed them, and we'd done everything in our power to try and find these people, we were then allowed to discard the embryos. We were, however, not allowed to use them for any other thing like research. So the consent form should include all these things. There was a famous case of a couple in Australia, way back when embryo freezing began, who died in a plane crash and had embryos frozen, and they happened to be very wealthy. The question is what inheritance rights did these embryos have and who was going to get the embryos? Are they going to be allowed to be thawed? There was a big hoopla in Australia. It actually caused them to stop doing embryo freezing for several months before they could sort out some of the issues. Divorce, separation, very common in this country, very common. So it needs to be discussed beforehand. If we get divorced what's going to happen to these embryos.

One of the ways to keep track of these people is to charge them a fee every few months, which most programs do. If you freeze embryos for a fee, that fee includes one-year storage. That allows you to have a baby and come back and get your embryos if you want a second baby from the same cycle of in vitro fertilization. But if you charge a storage fee at least hopefully, you keep up with where the couple is located so it gives you a way to track these people so that you know where they are.

There have been several cases in the United States where the couples couldn't agree. The judges get involved to decide on who, who gets to have the baby or not have the baby. It's a very big problem. I had an interesting personal anecdote. I took care of a 27-year-old woman who had breast cancer. She was engaged to a young man and they came to see me just before she had breast cancer diagnosed. She had a mastectomy, she was going to have major duty chemotherapy, had a 99 percent chance of losing her ovarian function. They were engaged to be married. They came to see me, and they said, "you know, we really want to do this". Well, number one, the impact of giving these drugs to people with breast cancer is not known, so we had to discuss that. This was before egg freezing was even feasible or thought about. This was about eight years ago, and we went ahead and did IVF on this couple. They got married and she actually did very well for the first couple of years. Then she had a recurrence of the breast cancer.

Well, we had eight embryos frozen and I had been thinking about her. I hadn't heard from her in a long time, so I tried to track her down about three years after we had done this. It turned out that she had passed away, and here were eight embryos that no longer had a mother. I eventually got hold of the husband who said that yes indeed she had had a recurrence. It was very sad. She'd just passed away six months before and here are these eight embryos. I said to him "What are we going to do with these embryos?" He said, "I don't want to throw them away, I want to keep them and I hope that someday that I marry someone who's going to be understanding enough to allow me to put these embryos into her." I said, "Oh my God." This is a true story.

This is the kind of thing that we have to think about with this technology. That's been about five years ago, and I moved and changed programs, so I don't know what happened in that case. Options are very important to be discussed. Thaw for transfer, thaw without the transfer, donate to a couple or donate to research? All those things need to be clarified.

Here we have egg donation and I'm going to change topics for a minute. Lynn already showed you that women over 40 tend to use egg donations more and more. This is a slide from Mark Sauer who is at Columbia Presbyterian, who is one of the gurus in egg donation in this country. He happened to have trained with me in the early '80s in California. This shows that the demand for egg donation has actually gone up for older women. I know we try to prevent teen pregnancy, but I think we're going a little bit too far the other way by letting women forget that they ought to reproduce between 25 and 35.
We need social changes, and I see all the young women laughing in the audience. We need some sort of social change that allows women to have careers or whatever. But they need to make time and not to forget about it. It's amazing how often I see in my office a couple who have been married ten years and the wife is 43 and, a year ago they decided maybe it was time to get pregnant. Duh. They didn't realize, and that irritates the heck out of me, and I feel bad for them, because this is very traumatic to go through. The very important message here, I think, is that women ought to try to reproduce, if feasible, when they can. Not everybody waits to find Mr. Wonderful until they are 38.

What about egg donation? Well there's a lot of issues with egg donation and this is very near to my heart since I've been doing it for so, so long. The first is where do you get the eggs? There are a lot of programs in the United States that use their own IVF patients as egg donors. In my program, we don't do IVF egg sharing. You can use a known egg donor, and that has incredible implications. A number of egg donors, a number of women bring me their sisters, their cousins. I've even had requests for mothers to use their daughters. 47 year old women wanting to use their 20 year old daughter's eggs. You can only imagine the complications with all of that. I think it's important, if we' re going to do all of that, that you have tremendous psychological assessment of the parties involved, and you need to have set rules in the beginning, okay? If your sister's going to donate eggs for you, how many times is she going to do it? What if it doesn't work the first time? If it works, what's her relationship going to be to the resulting child? All of these are incredibly complicated issues that should not be entered into lightly, okay?

So, there are a lot of relationship issues that have to be addressed. These things are a lot easier with anonymous people. However, the psychological issue of anonymous donation is that you don't have that connection. You're taking a risk. I, the doctor, have picked a donor for you who's been medically and psychologically screened. A person that's not a crazy person, that doesn't have three eyeballs. There are problems with each way we do egg donation.

I've actually had the experience of having a sister wanting to speak to me alone in my office, after I'd spoken to her and her sister who wanted to be the recipient. She begged me to figure out a way she could not donate eggs for her sister. She said to me, "My sister has always been a bully. She's always told me what to do, and I don't want to do this, but I don't know how to say no." We had to dream up some medical reason why she couldn't do it. You have to really confront this, and this opens up a whole Pandora's Box from a family point of view.

This can be a major problem. Again, the number of attempts, the potential implications for success or failure, and with a child, all those issues need to be addressed.

Now, there's a lot of legal uncertainties, and in some states, I had the honor of going to court in Virginia. It was a woman who was older, her eggs were okay, but she wasn't getting pregnant. We put her eggs; into a surrogate who was younger. She had a baby after many, many eggs, embryos were transferred. I had to go to court because the woman wanted her name, since she was the biologic mother, put on the birth certificate. The Commonwealth of Virginia said wait a minute, you didn't have this baby, you weren't the one that went through labor in the nine months. So, how can we do this? We actually had to go to court, and it gets really complicated, and the woman won, but the judge was so confused. It's like, oh, my God, what, explain this to me again. I was there, let me explain this to you. The interesting part was that, before he would change the name on the certificate, the judge wanted a home visit, like an adoption. This is true, even though the patient already had the baby because it had already been pre-arranged, we had an arrangement with this woman. It was the only way the .judge could relate to this.

So, whatever these issues are, are incredibly complicated. Now, the issue of compensation. Lynn already mentioned about the web site with the 15,000 dollar fee. You probably know about the famous ad in the paper for 50,000 dollars for an Ivy League student who had to stand a minimum of five ten tall, with an SAT score of 1,400, etc., etc. This becomes a major problem. There was a big battle in the city when one of the programs across the river, a very well known program, decided to double the fees that they pay the donors. The price used to be, when I lived in New York three years ago, 2,500 dollars per cycle, which was pretty good in terms of compensation for their time and effort.

The program was not getting any donors, so they decided to pay them $5,000. There were donors from mid-town Manhattan, in the middle of their IVF cycles, calling the clinic across the river to say, "I'm in the middle of my cycle. I want to come to you because you're going to pay me twice as much." So, these are very, very problematic issues. In certain countries, this is outlawed. For instance, in Canada, one cannot pay egg donors or sperm donors.

In Europe, as well as in France, first of all, in France, you cannot do this if your over 42. This leads to what we call reproductive tourism. A lot of patients have come to the United States because whatever the rules are in their particular countries - for instance, in England, you cannot transfer more than three embryos. I've had patients come to me from other countries with their frozen embryos saying, "I've already had multiple transfers of three. Here's my remaining seven embryos. I want you to transfer all of them." And they come to the United States to do that.

These are all very complicated issues, but it's not unusual to see these kinds of ads looking for and recruiting donors. Recruiting egg donors is a full-time job, and if you do a good job at it, it takes a lot of time to get one good donor. You hope they're not crazy. They will do what you say. They're not just doing it for the money. You really want to have somebody who is doing it for the right motivation, and has been shown that they do care. They want to help other people. A lot of these young women actually know people who are infertile, and that's the reason they get involved. It's okay if you're paying them 2,500 dollars, but if you're paying 50,000 dollars, then you have to wonder why they're doing it. Of course it could pay your college tuition in an Ivy League school.

Then another issue is who's too old to have egg donation. The Italians, actually, did the first woman over 60. There was a woman in California a few years ago, who lied. She looked young. She was Filipino and was actually 10 years older than she said she was. She got pregnant at presumably 54. She was actually 64, and did just fine and has a healthy baby. But the issue is, who has the right to decide this? Luckily, most patients over 50 generally have some sort of medical reason why it probably wouldn't be a good idea to get pregnant. That may be changing as the population gets healthier and healthier and lives longer and longer.

If you have any tendency to diabetes, high blood pressure, cardiac disease, it's not a good idea to get pregnant. A lot of times we get away with not allowing women, or not encouraging women to do this after 50. So who decides? The American Society for Reproductive Medicine, of which S.A.R.T, The Society for Assisted Reproductive Technology is an affiliate, has an ethics committee, and they have guidelines that we've published in 1994.

This just says that in most cases an adult's claim on rights to procreate via reproductive technology should be subjugated to the needs to children. I think one of the things you have to think about is if you're going to be 60 and have a child, that when that child's going to be 10 years old you're going to be 70. That child may be orphaned by the age of 12. You have to think of the social implications of that.

In situations where parental age, wellness and longevity are principal concerns, the well-being of children should be the dominant issue considered, which is actually kind of a departure for OB/GYNs. We always think about the mother first.

Now, one last thing I want to talk about, and that's posthumous reproduction because this actually happened. Two in the morning. I'm Director of Reproductive Technologies, Mt. Sinai Hospital, and I get a phone call from the urologist that I work with saying, there is a man who just had a cerebral bleed. I just got a phone call from an ICU in some hospital, not Mt. Sinai, and they want me to come and electro-ejaculate him to retrieve the sperm because his wife wants to freeze his sperm for later use because he's basically brain dead. Two in the morning, I'm like, hello? I'm asleep. Run that by me one more time. You have 24 hours because you're going to unplug him, and the more hypoxia he suffers, the more hypoxia to his testicles, the sperm are going to get worse. So, it's a problem.

You probably saw some of this in the media recently from a case in California. This is happening, and this is a major problem. How can we use posthumous reproduction? Well, I have done this. I have actually used sperm that has been frozen prior to the man dying. I had couples that were under care with me while the husband had been undergoing chemotherapy. He did well. They had a baby. Then she had sperm, and still wanted to have a second baby. She tried while he was alive. They gave up for a while because he got very sick. He died. She had some sperm left, and she said, I cannot throw this sperm away. I have to do something with the sperm one more time. Guess what? She had a baby. So, this does happen.

There was a famous case in England where they were not going to allow the woman to use her dead husband's sperm, and in France as well. There have been several cases in Europe, and the English authority prohibited it; England has an authority that regulates some of these technologies. The woman won the case, but she could not get that sperm to be used in England. So she had to again go across the continent and find somebody that would inseminate her with the sperm.

So, it can be done with sperm. It could be done with cryopreserved embryos if one of the parties dies, just as I mentioned with my patient with breast cancer, and the parties of the donors. If you have a man who is on a respirator, how do you know if he intended to reproduce? So, yes, if it were, as I mentioned, my infertility couple who were already in my office ahead of time, that's one story, but on the other hand, it's a problem.

One of the things people who have done this have decided is that there should be a grace period when the woman has art opportunity to grieve before she actually goes ahead and uses the sperm, to make sure that she really realizes what is intended. There has also been an interesting case of a wealthy couple whose son was young and had cancer. He had his sperm frozen, and then the young man died. The parents of the man, the grandparents of the intended child, wanted actually to use a surrogate to be able to have another child with the sperm. Who has a right to decide? The wishes of the deceased spouse should always be known and honored. The request to obtain sperm from terminally ill or recently deceased individuals without their prior consent need not be honored. Oftentimes you don't have the consent. If you're going to do it, I think a grace period for grieving is a good idea. In these, and other cases of posthumous reproduction, it is the responsibility of a specialist. Again, this is from the Ethics Committee to insist on full disclosure to all participants, to ascertain that all appropriate informed consents are obtained, and to insure adequate screening and counseling of all concerned parties. You cannot counsel a man on a respirator. So, this becomes very difficult.

Now, why do these services cause so much media attention? First of all, the importance of families and children, not only our culture, but in just about every culture, is important. There's the ethical issue that I've just mentioned, which obviously should and does generate a great deal of public debate. There's the cost of IVF services, particularly since it's not covered by most health insurance.

Infertility, we've heard already today from someone who was affected personally, can be devastating. It's not high priority to society in general, because we always talk about too many people in the world, but these people who really want a child are devastated by their condition. We want singleton children and hopefully some of these technologies will get us there. I think we have to think about the hierarchy of interest.

The people whose interests should be highest on our minds are those people who are affected by the condition. I think government agencies and professional organizations should be farther removed from decision making. We're not the primary motivators here, but the results of what we do is most important to those people that we treat.

And then the largest question, I think the hardest sometimes for couples is, when do you stop? This is a major issue, and particularly now that we have so many options. Is 40 long enough? 45? 50? When do you stop in terms of age, and when do you stop in terms of depleting your emotional and financial resources? It is okay, in my opinion, to allow people to stop. I give people permission to say enough is enough. Adoption is a wonderful option if they want to do that. For some people, however, adoption is not a wonderful option, and so they either continue or choose to lead a childless existence, which is perfectly fine.

This is a very critical issue that I think often gets neglected. In the enthusiasm to help people, we forget sometimes that it's best to help them to stop trying to be helped.

SONNY FOX: Thank you, Dr. Bustillo. I want to take a couple of minutes because, my goodness, have we raised issues with this. Does anybody have something they want to ask Dr. Bustillo or Dr. Wilcox about any of these issues out here? I heard echoes of the Master Race in there, the harvesting of embryos. I want to talk to you about that for a minute.

When you implant there are two pressures. One is, you don't want to have too many embryos because that'll lead to multiple births. Yet, if somebody is paying 15 grand for the cycle, they want to get the maximum, so you just put eight embryos to maximize the chance of getting pregnant. Embryos are impregnated. Who has the call on whether they have all the children, or one, or two, or what? How does that work, and what are the issues?

DR. MARIA BUSTILLO: First of all, who has the right to decide how many embryos are put back? In England, if I put back four embryos in a 40 year old, which I do routinely in America, I would go to jail, get my license yanked. I wouldn't get reimbursed for doing in-vitro fertilization. In certain countries, in Germany, you can only inseminate three eggs. It solves that problem. So in different countries there are different regulations. In America, in general, our professional society has been against having those regulations because it's patient-specific.

So, what we try to do is look at our own data and our own program, and now we have guidelines. If the person is very, very young with very good prognosis of getting pregnant, probably, they should only have two, and at most, three embryos. You do compromise your pregnancy rate. We know that in Europe, for instance, instead of one in four women taking home a baby, it's probably more like one in five, one in six per try. Of course if insurance covers that, they don't have, perhaps, as much pressure of getting pregnant from the first cycle.

SONNY FOX: But the other part of the question is if you have several embryos, how do you decide?

DR. MARIA BUSTILLO: Yes. How do you decide how many to put back? It's a clinical decision, but it's a decision that has to be made with a couple. Two things happen, at least in my practice. The embryologist who looks at embryos everyday, and the physician doing the embryo transfer will discuss things with the couple. We actually take pictures of the embryos and say, "These are your embryos. This one looks great. This one doesn't look so good, etc."

We suggest that, at your age, because of your condition, what you've done before, since this is your third IVF cycle, that you have X number of embryos transferred. The couple can say, forget it. I have six embryos. I want all six of them back. What do I do then? I have to do it. Usually they sign a consent form saying they understand the risks of multiple pregnancy. Sometimes they come back with quadruplets, though not very often because these are poor-prognosis patients. So, it's a mutual decision between the two.

Now, if you conceive a pregnancy of more than three, who has the right to decide how many will be born? It's up to the couple. At that point though pregnancy, over three particularly, is very morbid in terms of effects on the mother and effects on the baby, as Lynn already mentioned. So, in general, the medical indications for selective reduction, as we call it, is whatever fetus you can get to easiest is terminated. It's like a partial abortion. It can be done for patients who have quadruplets or more, or even for patients who have triplets or more.

Patients freak out sometimes if they have twins and want to have a reduction from two to one, which is not necessarily medically justified, but might be psychologically justified. The couples have to decide that. In most places, those of us who helped create these pregnancies do not deal with that, which is kind of interesting. Our perinatal colleagues are the ones that are dealing with that, so it makes it hard sometimes to get the data. Concerning selective reduction, we don't have any data. I think the CDC and S.A.R.T. is going to be looking at that a little bit more carefully in the next few years.

DR. LYNN WILCOX: I was just going to note that in about a month we're going to be releasing a report, through the Journal of The American Medical Association, looking at the risk of transferring a certain number of embryos at a certain age under various circumstances. I suspect there'll be a lot more discussion at that point about what are the appropriate numbers. We've already shared that data with the Society for Assisted Reproduction Technology, and they're revising their guidelines based on some of this information.

SONNY FOX: Concerning the auction site for the eggs at 50,000 dollars, or the description of the racial or other characteristics that you want in your egg donor. Are there any government regulations in that regard, or are they being contemplated?

DR. LYNN WILCOX: They're not in at the federal level. I don't believe they're in at the state level either.

SONNY FOX: Are they being contemplated, in terms of regulating egg donors?

DR. MARIA BUSTILLO: At present, that would be considered regulating medical practice, which is not generally done.

SONNY FOX: Okay. Anybody have any other questions?

MALE: Yeah, I'm curious. You talked about gender selection, Is that more for boys or more for girls?

SONNY FOX: If you take a look at the reports from China, for instance, at the ratio of men to women, children or men to women period, you'll find that each year it increases. It's now about 120 men to 100 woman. What do we have in this country, Dr. Bustillo?
DR. MARIA BUSTILLO: At birth, there are slightly more men then women.
SONNY FOX: Slightly more, but 120 to a 100 is extraordinary.

DR. MARIA BUSTILLO: Yeah, yeah.

SONNY FOX: That is what we know is going on in China, either that or they have other ways of disposing of the children - the girl children, or they will do it selectively by identifying the sex of the child and aborting. Especially with this pressure to have one or only two children. So, they want to make sure they have a boy.

DR. MARIA BUSTILLO: I think some data in the United States shows it's an equal number that want girls and boys, depending on what they've had before. It depends on whether it's a genetic condition for which they would do better to have a girl baby because it's an X linked disorder. This preliminary data looks like we're a little more biased.

SONNY FOX: Do you worry that the improvements and the technology that will allow sex selection to become easier and easier will exacerbate that problem?

DR. MARIA BUSTILLO: Yes, I do.

SONNY FOX: Any suggestions how we approach that?

DR. MARIA BUSTILLO: I don't know. That's one way to approach it. I will not accept donors that somebody's paying 50,000 dollars to. I will not do those couples, and I don't do family balancing for non-genetic reasons. So, that's one way to handle it, but, you know, somebody's going to and make a profit out of it. So, it's a problem because it's going from a medical service to commodifying some of these things. That's where the lines get really blurry. I don't know whether it's going to be our professional organizations, or consumers, the world, or the public, who's going to lead the charge on some of these things, but yes, I worry. I was at that clinic, and that was one of the reasons I left that clinic.

SONNY FOX: It seems to me that we have this in other areas of our lives today that the technology gives us almost the role of playing God in terms of fertility. We are an organization that speaks to the problem of unwanted children, of unplanned pregnancy, of trying to get people to avoid unplanned pregnancies, but we' re not saying don't have children. We're really saying have the children you want when you want them. Space them properly and so on. That's the way we approach the population issue. Here, we're dealing with an entirely different prospect which is people who desperately want a child anti the technology that's at their behest, and you don't want to deny them that, but it sure does bring up some interesting psychological and ethical questions. I would think that for a scriptwriter, it might be some area that you might want to think about because it certainly would play out for a long period of time in a script. Thank you both very, very much. Thank you.